"End-Stage" Neurofibrillary Tangle Pathology in Preclinical Alzheimer's Disease: Fact or Fiction?
"End-Stage" Neurofibrillary Tangle Pathology in Preclinical Alzheimer's Disease: Fact or Fiction?
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DOI：
10.3233/jad-2011-101980
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Nelson, Peter T.
中科院分区：
文献类型：
--
作者：
Abner, Erin L.;Kryscio, Richard J.;Nelson, Peter T.
在死前认知完好无损的人中，尸检可能会发现一些阿尔茨海默病类型的病理。在认知完好的人中存在终末期病理将支持病理标记物是附属物的假说。我们评估了晚期神经原纤维(Braak期V和VI期)病理，重点是非痴呆患者。分析了来自国家阿尔茨海默氏症协调中心数据库(最初包括4,690人)和NUN研究(最初包括526人)的数据，每个病例都有关于全球认知的生前信息和仔细的尸检研究。整体认知(最终简易智力状态检查分数[MMSE]和临床‘痴呆’状态)与神经病理学相关，包括神经原纤维病变的严重程度(Braak分期和大脑新皮质神经原纤维缠结计数)。分析支持三个主要发现：1.Braak V期病例和Braak VI期病例在相关生前认知方面存在显著差异；2.根据缠绕计数，Braak VI期病例存在明显的病理范围，因此新皮质中神经原纤维缠绕最多的大脑总是有严重的生前认知障碍；3.没有非痴呆症病例在一年内最终MMSE评分为30分，Braak VI期病理。合并Braak V期和VI期病例可能是不合适的，特别是在早期认知功能障碍的患者中，因为这两个病理阶段在病理严重程度和生前认知状态方面似乎都有很大的不同。目前尚无真正的终末期神经原纤维病变与完整认知共存的文献记载。
Among individuals who were cognitively intact before death, autopsies may reveal some Alzheimer's disease-type pathology. The presence of end-stage pathology in cognitively intact persons would support the hypothesis that pathological markers are epiphenomena. We assessed advanced neurofibrillary (Braak stages V and VI) pathology focusing on nondemented individuals. Data from the National Alzheimer's Coordinating Center database (n = 4,690 included initially) and from the Nun Study (n = 526 included initially) were analyzed, with antemortem information about global cognition and careful postmortem studies available from each case. Global cognition (final Mini-Mental State Examination scores [MMSE] and clinical 'dementia' status) was correlated with neuropathology, including the severity of neurofibrillary pathology (Braak stages and neurofibrillary tangle counts in cerebral neocortex). Analyses support three major findings: 1. Braak stage V cases and Braak VI cases are significantly different from each other in terms of associated antemortem cognition; 2. There is an appreciable range of pathology within the category of Braak stage VI based on tangle counts such that brains with the most neurofibrillary tangles in neocortex always had profound antemortem cognitive impairment; and 3. There was no nondemented case with final MMSE score of 30 within a year of life and Braak stage VI pathology. It may be inappropriate to combine Braak stages V and VI cases, particularly in patients with early cognitive dysfunction, since the two pathological stages appear to differ dramatically in terms of both pathological severity and antemortem cognitive status. There is no documented example of truly end-stage neurofibrillary pathology coexisting with intact cognition.